European Thyroid Journal最新文献

Objective: to evaluate differences in clinical presentation, diagnostic and therapeutic modalities, and outcomes in two cohorts of patients with sporadic medullary thyroid carcinoma (MTC) from reference centres in Italy and the Netherlands. The two centres have different diagnostic approaches, including the use of routine calcitonin (CT) measurement.

Methods: a total of 165 patients (106 Italian and 59 Dutch) were retrospectively included. The cohorts were compared overall and according to diagnostic modality. Logistic regression and multivariable Cox proportional hazards models were used, as appropriate, to assess progression-free survival (PFS), disease-specific survival (DSS), and associated risk factors.

Results: the Dutch cohort presented with more advanced disease, as per higher TNM, AJCC staging, and significantly higher CT both preoperative and at last visit (P <.001). Dutch patients received more frequently second operations, radiotherapy, and systemic treatments. PFS and 10-years DSS were significantly lower in the Dutch cohort (P<.001 and P.01). Tumour size, nodal involvement, presence of distant metastases at diagnosis and progression during the follow-up were independent strong predictors of shorter PFS and DSS. Patients diagnosed via routine CT measurement showed a less aggressive presentation and more favourable outcome.

Conclusions: We compared for the first time two MTC cohorts from Countries with different diagnostic and therapeutic approaches. Our data contribute to highlight an association between routine CT measurement and MTC presentation and outcome, while suggests that caution should be paid when interpreting the differences among Countries in MTC prevalence and clinical features.

Objective: Given the limitations of conventional approaches in managing indeterminate thyroid nodules, there remains an unmet need for non-invasive assistant tools to improve risk stratification. This study aimed to evaluate the clinical applicability of an artificial intelligence (AI) model for thyroid nodules with atypia of undetermined significance (AUS) cytology.

Methods: We retrospectively reviewed patients who underwent fine-needle aspiration (FNA) for thyroid nodules between January 2019 and December 2020 across five medical institutions in Korea. Nodules initially diagnosed as AUS and later confirmed as benign or malignant were included. A previously developed deep learning-based AI model, AI-Thyroid, was employed to provide binary classifications (benign or malignant) and malignancy risk estimates.

Results: A total of 165 thyroid nodules were analyzed. The median (interquartile range) longest diameter was 1.30 cm (0.80-2.10), and the malignancy rate of the cohort was 39%. In binary classification tasks, the model achieved a sensitivity of 0.91 and a negative predictive value of 0.87. The area under the curve (AUC) based on estimated malignancy risk was 0.75 (95% confidence interval (CI): 0.68-0.83), and the AUC derived from K-TIRADS categories 2-5 was 0.76 (95% CI: 0.69-0.83), indicating comparable diagnostic accuracy with the traditional scoring system. Subgroup analyses demonstrated that the model achieved a sensitivity of 98% in nodules smaller than 1.5 cm.

Conclusion: AI-assisted ultrasound analysis offers supplementary diagnostic information for thyroid nodules with AUS cytology. Its high sensitivity and negative predictive value may assist clinicians in decision-making processes, particularly for small, low-risk thyroid nodules.

Background: Significant progress has been made in the management of Thyroid eye disease (TED), based on the elucidation of important pathogenic mechanisms. This has led to novel therapeutics validated in randomized clinical trials. Autoreactive antigens that elicit specific orbital immune reactions have not yet been identified, although it has been shown that fibrocytes, circulating stem cells which differentiate into fibroblasts, are expressing the thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor-1 receptor (IGF-1R) and may be stimulated in the orbit by a cascade of inflammatory reactions inducing adipogenesis.

Ted clinical assessment: Moderate-severe forms of TED are the target for immune suppressive therapy. Improvement in the assessment of the active and progressive phase of disease is becoming compelling, as the outcome of a treatment depends on how early during the progressive phase the disease is treated. The clinical activity score may not always help define the right time for treating.

Therapy: In 2020 teprotumumab, an anti-IGF-1 receptor blocker, has been FDA approved for the treatment of TED. Since then other drugs were studied or are under investigation and will seek regulatory approval.

Microbiome and ted: A series of studies have investigated the role of microbiome in thyroid autoimmunity and TED more in detail, based on the observation that treatment with antibiotics may modify the disease phenotype in a murine model of TED.

Artificial intelligence: This approach is being studied for the assessment of TED, especially trying to standardize the use of orbital and facial images for improving the diagnosis of the disease in the early, progressive phase. In the future these applications will allow the use of synthetic data, in addition to training on real patient images and data.

Background: Paediatric and young adult differentiated thyroid carcinoma (DTC) often presents at an advanced stage but carries an excellent prognosis. While age-related genomic differences from adult DTC are recognized, it remains unclear whether outcomes are driven by age or tumour biology.

Methods: We analysed a multi-institutional cohort of 363 patients aged 0-25 years who underwent molecular testing and surgical management. Age was categorized using cut-offs at ≤8, 9-14, 15-18, and 19-25 years. The primary endpoint was disease status at last follow-up, categorized according to American Thyroid Association (ATA) response criteria. Multivariable ordered logistic regression was used to test the independent prognostic effect of somatic driver mutations while adjusting for age, sex, and follow-up duration.

Results: Distinct age-related patterns of oncogenic drivers were observed: RET and NTRK1/3 fusions were predominant in younger patients, BRAF V600E was most frequent in adolescents, and RAS mutations were enriched in young adults. After adjustment, driver mutations independently predicted long-term outcomes. NTRK1/3 fusions (aOR = 5.29, 95% CI: 1.77-15.79), BRAF V600E (aOR = 3.45, 95% CI: 1.37-8.70), and RET fusions (aOR = 3.34, 95% CI: 1.13-9.90) were associated with significantly higher odds of a non-excellent outcome. Conversely, RAS mutations showed a favourable trend, and all DICER1-mutant cases achieved excellent outcomes. While prognosis steadily improved with age, mutation status remained the dominant factor determining outcomes.

Conclusion: Somatic drivers offer prognostic insights independent of age in paediatric and young adult DTC, establishing a molecular framework for precision risk stratification that complements traditional clinical staging and age-based assessments.

Objective: Thyrotropin receptor antibodies (TRAbs) are central to Graves' disease management, but their long-term kinetics after total thyroidectomy is poorly defined. We aimed to describe long-term TRAb trajectories and identify predictors of decline using clinically relevant thresholds.

Methods: TRAb levels were measured serially in 1,516 patients after total thyroidectomy. Primary outcomes were time to TRAb < 10 and <2 IU/L, corresponding to a pragmatic fetal-risk threshold and assay negativity, respectively. Clinical factors (age, sex, body mass index, smoking, preoperative TRAb, and thyroid weight) were evaluated using Kaplan-Meier analyses and multivariable logistic regression.

Results: TRAb levels declined rapidly, with median values falling below 10 IU/L within 2 years. Among patients with preoperative TRAb ≥ 10 IU/L, 84.8% reached <10 IU/L and 60.1% reached <2 IU/L within 5 years. In multivariable models, younger age, lower preoperative TRAb, and smaller thyroid weight independently predicted earlier decline, whereas sex, body mass index, and smoking did not.

Conclusions: In this large post-operative cohort, younger age emerged as an independent predictor of accelerated TRAb decline after total thyroidectomy. Total thyroidectomy yields sustained TRAb decline and may promote immunological remission, particularly in younger patients, by removing the antigenic source before the establishment of long-lived plasma cells. These findings highlight age as a key determinant of TRAb kinetics and provide timelines for counselling and follow-up. Surgery may be especially valuable when a timely TRAb decline is required, such as in younger patients planning pregnancy or those with orbitopathy or antithyroid drug refractoriness.

European iodine fortification programmes are heterogeneous and in some countries ineffective. A key problem with iodine nutrition is the low awareness of iodine deficiency-related risks common in the general population and among women of reproductive age. The major objective of EUthyroid2 is to improve the low awareness of IDD risks in adolescents and young women. The aim is to identify best practice models for accessing and disseminating information to increase awareness and improve iodine status, thereby establishing a foundation for young women to improve their own thyroid function, their general health and that of their offspring. To achieve this, EUthyroid2 will build on existing infrastructures and expertise established by the consortium during the initial EUthyroid project. All interventions tested will be tailored to specific regions and populations. EUthyroid2, by identifying the most effective intervention tools, will establish a solid foundation for paving the way for future national awareness campaigns.

Purpose: We examined the effect of selenium vs placebo on remission rate and quality of life (QoL) in the Graves' selenium supplementation (GRASS) trial (ID: NCT01611896).

Methods: Double-blinded, placebo-controlled, multi-centre trial in individuals with newly diagnosed Graves' hyperthyroidism randomised to daily supplementation with 200 μg selenium or placebo tablets during 24-30 months, depending on the timing of antithyroid drug (ATD) withdrawal. The primary outcome was the proportion of participants with non-remission, defined as receiving ATD or remaining hyperthyroid (thyroid stimulating hormone <0.1 mIU/L) during the last 12 months of the intervention period or referral to ablative therapy (radioactive iodine or surgery). QoL was serially assessed by the thyroid-related patient-reported outcome ThyPRO and compared with previously collected norm data.

Results: Between Dec 7th 2012 and Dec 3rd 2018, 430 participants with Graves' hyperthyroidism were recruited. Non-remission was observed in 114 (53.3%) participants in the placebo group and 118 (54.6%) in the selenium group (OR = 1.0 (95% CI: 0.7-1.5); P = 0.98). There was no beneficial effect of selenium, as compared with placebo, on any ThyPRO scale. The participants' QoL at the end of the study was comparable to that of the general population sample. Thyrotropin receptor antibody levels were similar in the groups at the 18-month and end-of-study follow-up visits.

Conclusion: In individuals with newly diagnosed Graves' hyperthyroidism, daily supplementation with selenium did not have any effects compared with placebo as add-on to standard antithyroid drugs. The GRASS trial findings do not support the use of selenium supplementation in Graves' hyperthyroidism.

This review explores the role of BRAF V600E in thyroid cancer with emphasis on its debated prognostic value, notable molecular heterogeneity, and opportunities as a therapeutic target. BRAF V600E, the most common oncogenic driver in papillary thyroid carcinoma, activates the MAPK pathway and suppresses genes involved in iodine metabolism and differentiation. While linked to adverse features and outcomes such as extrathyroidal extension, lymph node metastasis, recurrence, and mortality, its utility as an independent prognostic marker remains controversial. In solitary intrathyroidal tumors (1-4 cm) and low-risk microcarcinomas, BRAF V600E testing may help refine surgical decisions, though evidence is inconsistent, particularly for tumors <2 cm. The mutation also contributes to radioactive iodine (RAI) refractoriness, but not all BRAF-mutant tumors behave similarly. Transcriptomic and genomic heterogeneity - including differences in thyroid differentiation score, genetic co-alterations and miRNA signatures - modulates treatment response. Targeting BRAF V600E has led to novel therapeutic strategies. Selective BRAF and MEK inhibitors - including vemurafenib, dabrafenib, and selumetinib - have demonstrated efficacy in advanced thyroid cancers. The combination of dabrafenib and trametinib is FDA approved for BRAF V600E-mutant anaplastic thyroid carcinoma based on its significant survival benefits. Moreover, due to its histology-agnostic approval for solid tumors with BRAF V600E mutations, this regimen is now also indicated for papillary and poorly differentiated thyroid cancers. In addition, redifferentiation strategies using MAPK inhibitors to restore RAI avidity have shown promise, particularly in selected patients. These advances highlight the need to contextualize BRAF mutation status within a broader molecular and clinical framework to guide personalized, effective treatment strategies.